The major goal of this program project is to investigate the immunogenetic basis of demyelination and neurological deficits. The experiments will utilize two excellent models of human multiple sclerosis, i.e. Theiler's virus infection and experimental autoimmune encephalomyelitis. The program project is under the direction of Dr. Moses Rodriguez Professor of Neurology and Immunology of the Mayo Medical School who has ha a long interest in the pathogenesis of demyelination and remyelination in human multiple sclerosis. Members of the Program Project (Drs. Chella S. David, Dr. Larry R. Pease, and Dr. Moses Rodriguez) are well established investigators and Professors of Immunology in the Mayo Medical School. This group has an impressive record of investigations on the immunogenetics in murine models of human disease. Project 1: (Dr. Rodriguez, Principal Investigator) will investigate transgenic expression of Theiler's virus genomes in mice. The experiments will also investigate the mechanisms of decreased demyelinating disease observed in human HLA transgenic mice and address the specificity of the pathogenic immune response important in development of functional neurological deficits following demyelination. Project 2: (Dr. Pease, Principal Investigator) will investigate the basis for H-2K vs. H-2D polarity of anti-TMEV lymphocyte responses in the central nervous system. Experiments will identify the importance of virus-specific CD8+ T cells in the resistance to persistence virus infection and in neuropathology. Project 3: (Dr. David, Principal Investigator) will investigate experimental autoimmune encephalomyelitis in HLA expressing HLA-DR or DQ haplotypes. Experiments will examine the presentation of putative autoantigens linked to MS by HLA-DR and DQ molecules. This Program Project focusing on the immunogenetic basis of demyelination by a group of highly interactive investigators is expected to provide new insights into the pathogenesis of myelin and neural injury in multiple sclerosis.